INTEGRATED ANALYSIS: OUTCOMES OF IBRUTINIB‐TREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LEUKEMIA (CLL/SLL) WITH HIGH‐RISK PROGNOSTIC FACTORS
Bibliographic record
Abstract
Introduction: In phase 3 studies, ibrutinib (ibr) was superior to ofatumumab in relapsed/refractory (R/R) CLL/SLL or chlorambucil in treatment (tx)-naïve (TN) CLL/SLL. Ibr + bendamustine/rituximab (BR) was superior to BR in R/R CLL/SLL. Clinical outcomes of pts in these 3 studies were examined to determine the impact of certain prognostic risk factors other than del17p. Methods: RESONATE: R/R CLL/SLL, ibr 420 mg/d until progressive disease (PD) or ofatumumab (≤24 wk). RESONATE-2: TN CLL/SLL (no del17p) ≥65 y, ibr 420 mg/d until PD or chlorambucil (≤12 cycles). HELIOS: R/R CLL/SLL (no del17p), BR (≤6 cycles) ± ibr 420 mg/d followed by ibr or placebo until PD. Data from 3 studies (N = 1238) were pooled to analyze outcomes with/without genomic risk factors IGHV, del11q, trisomy 12, or complex karyotype (CK). Covariates for a multivariate analysis (MVA) for progression-free and overall survival (PFS, OS): the 4 genomic risk factors, age, sex, ECOG PS, cytopenias, LDH, bulky disease, and number of prior therapies. Results: Median follow-up was 21 mo for both ibr- and comparator-tx pts. In each subgroup, PFS, OS, and response rates were higher in ibr- than comparator-tx pts, regardless of these genomic risk factors. By univariate analysis (UVA, Table) in ibr-tx pts, genomic risk factors were not associated with shorter PFS or OS, and del11q was associated with a trend of longer PFS and OS. In comparator-tx pts, unmutated (U)-IGHV, del11q, and CK were associated with shorter PFS, and U-IGHV and CK with shorter OS. By MVA for PFS/OS, in ibr-tx pts (without del17p), only ≥1 prior tx was associated with shorter PFS and OS. Age ≥ 65 and elevated LDH were associated with shorter OS, and del11q with a trend of longer OS. In comparator-tx pts, ≥1 prior tx, U-IGHV, del11q, CK, male sex, and bulky disease ≥5 cm were associated with shorter PFS; CK, male sex, bulky disease ≥5 cm, ECOG PS ≥1 and elevated LDH were associated with shorter OS. Cumulative rates of adverse events were similar in pts with/without genomic factors and reflect a median exposure of 19-20 mo for ibr-tx pts and 5-10 mo for comparator-tx pts. Conclusions: In UVA and MVA for ibr-tx pts, no clear associations were found for U-IGHV, del11q, trisomy 12, and CK with poor outcomes; del11q associated with trends of longer PFS and OS in UVA, and longer OS in MVA. In comparator-tx pts, U-IGHV, del11q, and CK associated with shorter PFS, OS, and/or lower response rate. Results suggest that risk factors associated with poor outcomes with chemotherapy have less relevance with ibr. CRR, complete response rate; HR, hazard ratio; NE, not evaluable; OR, odds ratio; ORR, overall response rate. *For IGHV, indicates mutated IGHV. **18 mo PFS rate was 8%. Keywords: chronic lymphocytic leukemia (CLL); ibrutinib; small lymphocytic lymphoma (SLL).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".